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Coenzyme A

ser - protein. Coenzyme A. Pantothenate. 2-mercaptoethylamine. ADP. Acyl carrier protein. Fritz Lipmann. Noble prize for Chemistry 1953 (shared with Sir Hans Krebs). "for his discovery of co-enzyme A and its importance for intermediary metabolism". 1899-1986. Pyruvate dehydrogenase.

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Coenzyme A

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  1. ser - protein Coenzyme A Pantothenate 2-mercaptoethylamine ADP Acyl carrier protein

  2. Fritz Lipmann Noble prize for Chemistry 1953 (shared with Sir Hans Krebs) "for his discovery of co-enzyme A and its importance for intermediary metabolism" 1899-1986

  3. Pyruvate dehydrogenase The core of the complex consists of 60 copies of E2. At the periphery of the complex are: • 30 copies of E1 (itself a tetramer with subunits a2b2) • 12 copies of E3 (a homodimer), plus 12 copies of an E3 binding protein that links E3 to E2.

  4. Pyruvate dehydrogenase OH OH O + + + 1. CO2 E1 TPP TPP-CH TPP-CH H+ H3C-C-COO- CH3 CH3 O O S – C –CH3 S – C –CH3 2. + E2 E2 + H+ E2 E2 E2 E2 O E2 + 3. + CoA-SH CoA-S - C –CH3 Acetyl CoA + FAD FADH2 FADH2 E3- E3- E3- + 4. FAD E3- S S SH SH S SH S SH SH SH + 5. + NADH + H+ NAD

  5. 1. Inhibited by AcCoA and NADH • AcCoA (competes with CoA for E2), • NADH (competes with NAD for E3) 2. Regulated by phosphorylation E2 is associated with PDH kinase and PDH phosphatase which act on E1 ·phosphorylation of the E1 subunit inhibits ·dephosphorylation activates. ·Phosphorylation controled by NADH/NAD, AcCoA/CoA and ATP/ADP. Increasing these ratios promotes phosphorylation and hence decreases activity. THEREFORE: Phosphorylation of E1 increases and activity of PDH decreases when energy charge is high. ·Pyruvate inhibits PDH kinase in the presence of high [ADP] and therefore promotes dephosphorylation and increase in activity. ·In muscle high [Ca2+] activates phosphatase. At onset of exercise [Ca2+], pyruvate and ADP increase resulting in increased PDH phosphatase (Ca) and decrease PDH kinase due to increased pyruvate + ADP, and decreased ATP/ADP ratio. Regulation of PDH:

  6. Sir Hans Krebs Noble Prize for Chemistry "for his discovery of the citric acid cycle" 1900 - 1981

  7. or GTP

  8. COO- SCoA O C COO- C O C H COO- C H2 CH3 COO- HO CH HO C COO- HC H C H2 COO- COO- COO- COO- C H2 H C H C COO- C H C H HO COO- COO- COO- COO- C H2 COO- C H2 C H2 C H2 COO- H C H COO- H C H O C C O COO- C O C H COO- COO- C H2 SCoA COO- HO CH HO C COO- HC H C H2 COO- COO- COO- COO- C H2 COO- H C H C COO- O C COO- C H C H HO C H COO- C H2 COO- COO- COO- HO CH HO C COO- HC H C H2 COO- COO- COO- COO- C H2 COO- C H2 C H2 C H2 COO- H C H COO- H C H COO- C O C H2 C O H C COO- H C COO- SCoA C H C H HO COO- COO- COO- COO- C H2 COO- C H2 C H2 C H2 H C H COO- H C H C O C O COO- SCoA Make a couple of copies of this for class

  9. O C O- Biotin + CO2

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